Generation ofde novomiRNAs from template switching during DNA replication

Autor: Heli A. M. Mönttinen, Mikko J. Frilander, Ari Löytynoja
Rok vydání: 2023
Popis: Micro-RNA (miRNA) genes represent one of the most constrained examples of genetic information found in metazoan genomes. All primary transcripts generated from these elements fold into a short RNA stem-loop structure that is further processed to a *22 bp dsRNA duplex. Incorporation of one of the strands into the RNA Induced Silencing complex (RISC) can then facilitate negative gene expression regulation. While a substantial number of miRNA genes are ancient and highly conserved, many are subject to rapid evolutionary change. Entirely novel miRNA genes have been shown to emerge in a lineage-specific manner in primates and plants. However, the specific mechanisms that generate these genetic elements have not been determined. Here, we show that up to 100 lineage-specific miRNA genes have emerged in primates via mutations caused by template switching during DNA replication. Template-switching mutations (TSMs) are complex mutations that can introduce in a single replication cycle inverted DNA repeats capable of forming perfect hairpin structures. Our findings demonstrate that TSMs are actively generating complex biological sequence variants which in suitable circumstances create miRNA genes from previously non-functional genomic sequences. This mechanism is orders of magnitude faster than others proposed for thede novocreation of genes, enabling near-instant rewiring of genetic information and rapid adaptation to changing environments.
Databáze: OpenAIRE